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New enzyme pathway to nerve cell death discovered in stroke and neurodegenerative diseases

LA JOLLA, CA. Scientists at The Burnham Institute report in this week's issue of Science magazine that an ephemeral gas, called nitric oxide, found in the body and as an air pollutant, can activate enzymes on the outside of nerve cells to trigger their demise during stroke and neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, and AIDS dementia. The enzymes belong to a family known as matrix metalloproteinases or MMPs. When activated in excess, these enzymes chew up the outside of nerve cells, resulting in their death.

"The new work uncovers the mechanism of activation of an enzymatic pathway that leads to nerve cell death," said Stuart A. Lipton, M.D., Ph.D., a neurologist who is Professor and Director of the Center for Neuroscience and Aging at The Burnham Institute, and head of the team reporting the new findings. "The MMP enzymes act outside of the nerve cell rather than inside," Lipton continued. Previously, the best characterized enzyme pathways that killed nerve cells were found inside nerve cells rather than outside. "The new results also link two previously unrelated scientific fields studying MMP enzymes and nitric oxide gas, both of which were thought to be important in the life and death of nerve cells, but the fact that nitric oxide [abbreviated NO] could activate these enzymes was not previously recognized," commented Lipton.

Using an intricate chemical approach called mass spectrometry, which allows precise characterization of proteins including enzymes, the scientists found that the MMP enzymes are not only activated by NO, but also that the MMPs are further affected by oxygen-related molecules to produce permanent and pathological activity of the enzymes, leading them to chew up the normal environment surrounding the nerve cell. This heightened activity occurs predominantly during periods of stress or disease, and results in the death of the nerve cells by a process known as apoptosis.

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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
15-Aug-2002


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